tbuckley/cabot-search huggingface dataset:
Electrical Impedance Tomography and Optimal Positive End-Expiratory Pressure: Uncovering Latent Heterogeneity of Treatment Effect
Authors: Jose Victor Jimenez, Robert C. Hyzy
Journal: American Journal of Respiratory and Critical Care Medicine (2023)

"Electrical Impedance Tomography and Optimal PEEP: Uncovering Latent Heterogeneity of Treatment Effect." American Journal of Respiratory and Critical Care Medicine, 0(ja), pp.
Finding Facts in Postacute Sequelae of COVID-19: Clinical, Radiographic, and Histopathologic Markers of Disease
Authors: Chiagozie I. Pickens, Benjamin D. Singer
Journal: American Journal of Respiratory and Critical Care Medicine (2023)

"Finding Facts in PASC: Clinical, Radiographic and Histopathologic Markers of Disease." American Journal of Respiratory and Critical Care Medicine, 0(ja), pp.
Elucidating the Underlying Mechanisms of the Marked Increase in Childhood Type 1 Diabetes During the COVID-19 Pandemic—The Diabetes Pandemic
Authors: Clemens Kamrath, Reinhard W. Holl, Joachim Rosenbauer
Journal: JAMA Network Open (2023)

Daniel D'Souza, BHSc; Jessica Empringham, MD; Petros Pechlivanoglou, PhD; Elizabeth M. Uleryk, MLS; Eyal Cohen, MD, MSc; Rayzel Shulman, MD, PhD
Design Parameters for Injectable Biopolymeric Hydrogels with Dynamic Covalent Chemistry Crosslinks
Authors: Narelli de Paiva Narciso, Renato S. Navarro, Aidan E. Gilchrist, Miriam L. M. Trigo, Giselle Aviles Rodriguez, Sarah C. Heilshorn
Journal: Advanced Healthcare Materials (2023)

Dynamic covalent chemistry (DCC) crosslinks can form hydrogels with tunable mechanical properties permissive to injectability and self-healing. However, not all hydrogels with transient crosslinks are easily extrudable. For this reason, two additional design parameters must be considered when formulating DCC-crosslinked hydrogels: 1) degree of functionalization (DoF) and 2) polymer molecular weight (MW). To investigate these parameters, hydrogels comprised of two recombinant biopolymers: 1) a hyaluronic acid (HA) modified with benzaldehyde and 2) an elastin-like protein (ELP) modified with hydrazine (ELP-HYD), are formulated. Several hydrogel families are synthesized with distinct HA MW and DoF while keeping the ELP-HYD component constant. The resulting hydrogels have a range of stiffnesses, G' ≈ 10-1000 Pa, and extrudability, which is attributed to the combined effects of DCC crosslinks and polymer entanglements. In general, lower MW formulations require lower forces for injectability, regardless of stiffness. Higher DoF formulations exhibit more rapid self-healing. Gel extrusion through a cannula (2 m length, 0.25 mm diameter) demonstrates the potential for minimally invasive delivery for future biomedical applications. In summary, this work highlights additional parameters that influence the injectability and network formation of DCC-crosslinked hydrogels and aims to guide future design of injectable hydrogels.
Imputation of low-coverage sequencing data from 150,119 UK Biobank genomes
Authors: Simone Rubinacci, Robin J. Hofmeister, Bárbara Sousa da Mota, Olivier Delaneau
Journal: Nature Genetics (2023)

Abstract The release of 150,119 UK Biobank sequences represents an unprecedented opportunity as a reference panel to impute low-coverage whole-genome sequencing data with high accuracy but current methods cannot cope with the size of the data. Here we introduce GLIMPSE2, a low-coverage whole-genome sequencing imputation method that scales sublinearly in both the number of samples and markers, achieving efficient whole-genome imputation from the UK Biobank reference panel while retaining high accuracy for ancient and modern genomes, particularly at rare variants and for very low-coverage samples.
Salivary biomarkers: novel noninvasive tools to diagnose chronic inflammation
Authors: Paola Dongiovanni, Marica Meroni, Sara Casati, Riccardo Goldoni, Douglas Vieira Thomaz, Nermin Seda Kehr, Daniela Galimberti, Massimo Del Fabbro, Gianluca M. Tartaglia
Journal: International Journal of Oral Science (2023)

Abstract Several chronic disorders including type 2 diabetes (T2D), obesity, heart disease and cancer are preceded by a state of chronic low-grade inflammation. Biomarkers for the early assessment of chronic disorders encompass acute phase proteins (APP), cytokines and chemokines, pro-inflammatory enzymes, lipids and oxidative stress mediators. These substances enter saliva through the blood flow and, in some cases, there is a close relation between their salivary and serum concentration. Saliva can be easily collected and stored with non-invasive and cost-saving procedures, and it is emerging the concept to use it for the detection of inflammatory biomarkers. To this purpose, the present review aims to discuss the advantages and challenges of using standard and cutting-edge techniques to discover salivary biomarkers which may be used in diagnosis/therapy of several chronic diseases with inflammatory consequences with the pursuit to possibly replace conventional paths with detectable soluble mediators in saliva. Specifically, the review describes the procedures used for saliva collection, the standard approaches for the measurement of salivary biomarkers and the novel methodological strategies such as biosensors to improve the quality of care for chronically affected patients.
A gene signature can predict risk of MGUS progressing to multiple myeloma
Authors: Fumou Sun, Yan Cheng, Jun Ying, David Mery, Samer Al Hadidi, Visanu Wanchai, Eric R. Siegel, Hongwei Xu, Dongzheng Gai, Timothy Cody Ashby, Clyde Bailey, Jin-Ran Chen, Carolina Schinke, Sharmilan Thanendrarajan, Maurizio Zangari, Siegfried Janz, Bart Barlogie, Frits Van Rhee, Guido Tricot, John D. Shaughnessy, Fenghuang Zhan
Journal: Journal of Hematology & Oncology (2023)

Abstract Multiple myeloma is preceded by monoclonal gammopathy of undetermined significance (MGUS). Serum markers are currently used to stratify MGUS patients into clinical risk groups. A molecular signature predicting MGUS progression has not been produced. We have explored the use of gene expression profiling to risk-stratify MGUS and developed an optimized signature based on large samples with long-term follow-up. Microarrays of plasma cell mRNA from 334 MGUS with stable disease and 40 MGUS that progressed to MM within 10 years, was used to define a molecular signature of MGUS risk. After a three-fold cross-validation analysis, the top thirty-six genes that appeared in each validation and maximized the concordance between risk score and MGUS progression were included in the gene signature (GS36). The GS36 accurately predicted MGUS progression (C-statistic is 0.928). An optimal cut-point for risk of progression by the GS36 score was found to be 0.7, which identified a subset of 61 patients with a 10-year progression probability of 54.1%. The remainder of the 313 patients had a probability of progression of only 2.2%. The sensitivity and specificity were 82.5% and 91.6%. Furthermore, combination of GS36, free light chain ratio and immunoparesis identified a subset of MGUS patients with 82.4% risk of progression to MM within 10 years. A gene expression signature combined with serum markers created a highly robust model for predicting risk of MGUS progression. These findings strongly support the inclusion of genomic analysis in the management of MGUS to identify patients who may benefit from more frequent monitoring.
Efficient and versatile multiplex prime editing in hexaploid wheat
Authors: Pei Ni, Yidi Zhao, Ximeng Zhou, Zehua Liu, Zhengwei Huang, Zhongfu Ni, Qixin Sun, Yuan Zong
Journal: Genome biology (2023)

Prime editing is limited by low efficiency in plants. Here, we develop an upgraded engineered plant prime editor in hexaploid wheat, ePPEplus, by introducing a V223A substitution into reverse transcriptase in the ePPEmax* architecture. ePPEplus enhances the efficiency by an average 33.0-fold and 6.4-fold compared to the original PPE and ePPE, respectively. Importantly, a robust multiplex prime editing platform is established for simultaneous editing of four to ten genes in protoplasts and up to eight genes in regenerated wheat plants at frequencies up to 74.5%, thus expanding the applicability of prime editors for stacking of multiple agronomic traits.
Association of Preoperative High-Intensity Interval Training With Cardiorespiratory Fitness and Postoperative Outcomes Among Adults Undergoing Major Surgery
Authors: Kari Clifford, John C. Woodfield, William Tait, Holly A. Campbell, James Chris Baldi
Journal: JAMA Network Open (2023)

Importance Preoperative high-intensity interval training (HIIT) is associated with improved cardiorespiratory fitness (CRF) and may improve surgical outcomes. Objective To summarize data from studies comparing the association of preoperative HIIT vs standard hospital care with preoperative CRF and postoperative outcomes. Data Sources Data sources included Medline, Embase, Cochrane Central Register of Controlled Trials Library, and Scopus databases with no language constraints, including abstracts and articles published before May 2023. Study Selection The databases were searched for randomized clinical trials and prospective cohort studies with HIIT protocols in adult patients undergoing major surgery. Thirty-four of 589 screened studies met initial selection criteria. Data Extraction and Synthesis A meta-analysis was performed according to Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines. Data were extracted by multiple independent observers and pooled in a random-effects model. Main Outcomes and Measures The primary outcome was change in CRF, as measured by either peak oxygen consumption (V̇ o 2 peak) or 6-Minute Walk Test (6MWT) distance. Secondary outcomes included postoperative complications; hospital length of stay (LOS); and changes in quality of life, anaerobic threshold, and peak power output. Results Twelve eligible studies including 832 patients were identified. Pooled results indicated several positive associations for HIIT when compared with standard care either on CRF (V̇ o 2 peak, 6MWT, anaerobic threshold, or peak power output) or postoperative outcomes (complications, LOS, quality of life), although there was significant heterogeneity in study results. In 8 studies including 627 patients, there was moderate-quality evidence of significant improvement in V̇ o 2 peak (cumulative mean difference, 2.59 mL/kg/min; 95% CI, 1.52-3.65 mL/kg/min; P &amp;amp;lt; .001). In 8 studies including 770 patients, there was moderate-quality evidence of a significant reduction in complications (odds ratio, 0.44; 95% CI, 0.32-0.60; P &amp;amp;lt; .001). There was no evidence that HIIT differed from standard care in hospital LOS (cumulative mean difference, −3.06 days; 95% CI, −6.41 to 0.29 days; P = .07). The analysis showed a high degree of heterogeneity in study outcomes and an overall low risk of bias. Conclusions and Relevance The results of this meta-analysis suggest that preoperative HIIT may be beneficial for surgical populations through the improvement of exercise capacity and reduced postoperative complications. These findings support including HIIT in prehabilitation programs before major surgery. The high degree of heterogeneity in both exercise protocols and study results supports the need for further prospective, well-designed studies.
USP51/PD‐L1/ITGB1‐deployed juxtacrine interaction plays a cell‐intrinsic role in promoting chemoresistant phenotypes in non‐small cell lung cancer
Authors: Jianjun Li, Xuechun Xiao, Yang Ou, Lixia Cao, Min Guo, Chunchun Qi, Zhaoyang Wang, Yuxin Liu, Qiuying Shuai, Hang Wang, Peiqing Sun, Yi Shi, Guang Yang, Shuang Yang
Journal: Cancer Communications (2023)

Abstract Background Programmed death ligand 1 (PD‐L1) has been demonstrated to facilitate tumor progression and therapeutic resistance in an immune‐independent manner. Nevertheless, the function and underlying signaling network(s) of cancer cell‐intrinsic PD‐L1 action remain largely unknown. Herein, we sought to better understand how ubiquitin‐specific peptidase 51 (USP51)/PD‐L1/integrin beta‐1 (ITGB1) signaling performs a cell‐intrinsic role in mediating chemotherapeutic resistance in non‐small cell lung cancer (NSCLC). Methods Western blotting and flow cytometry were employed for PD‐L1 detection in NSCLC cell lines. Coimmunoprecipitation and pulldown analyses, protein deubiquitination assay, tissue microarray, bioinformatic analysis and molecular biology methods were then used to determine the significance of PD‐L1 in NSCLC chemoresistance and associated signaling pathways in several different cell lines, mouse models and patient tissue samples. Ubiquitin‐7‐amido‐4‐methylcoumarin (Ub‐AMC)‐based deubiquitinase activity, cellular thermal shift and surface plasmon resonance (SPR) analyses were performed to investigate the activity of USP51 inhibitors. Results We provided evidence that cancer cell‐intrinsic PD‐L1 conferred the development of chemoresistance by directly binding to its membrane‐bound receptor ITGB1 in NSCLC. At the molecular level, PD‐L1/ITGB1 interaction subsequently activated the nuclear factor‐kappa B (NF‐κB) axis to elicit poor response to chemotherapy. We further determined USP51 as a bona fide deubiquitinase that targeted the deubiquitination and stabilization of the PD‐L1 protein in chemoresistant NSCLC cells. Clinically, we found a significant direct relationship between the USP51, PD‐L1 and ITGB1 contents in NSCLC patients with chemoresistant potency. The elevated USP51, PD‐L1 and ITGB1 levels were strongly associated with worse patient prognosis. Of note, we identified that a flavonoid compound dihydromyricetin (DHM) acted as a potential USP51 inhibitor and rendered NSCLC cells more sensitive to chemotherapy by targeting USP51‐dependent PD‐L1 ubiquitination and degradation in vitro and in vivo. Conclusions Together, our results demonstrated that the USP51/PD‐L1/ITGB1 network potentially contributes to the malignant progression and therapeutic resistance in NSCLC. This knowledge is beneficial to the future design of advanced cancer therapy.
Oncogenic ASPM Is a Regulatory Hub of Developmental and Stemness Signaling in Cancers
Authors: Kelvin K. Tsai, Byoung-Il Bae, Chung-Chi Hsu, Li-Hsin Cheng, Yuval Shaked
Journal: Cancer Research (2023)

Abstract Despite recent advances in molecularly targeted therapies and immunotherapies, the effective treatment of advanced-stage cancers remains a largely unmet clinical need. Identifying driver mechanisms of cancer aggressiveness can lay the groundwork for the development of breakthrough therapeutic strategies. Assembly factor for spindle microtubules (ASPM) was initially identified as a centrosomal protein that regulates neurogenesis and brain size. Mounting evidence has demonstrated the pleiotropic roles of ASPM in mitosis, cell-cycle progression, and DNA double-strand breaks (DSB) repair. Recently, the exon 18–preserved isoform 1 of ASPM has emerged as a critical regulator of cancer stemness and aggressiveness in various malignant tumor types. Here, we describe the domain compositions of ASPM and its transcript variants and overview their expression patterns and prognostic significance in cancers. A summary is provided of recent progress in the molecular elucidation of ASPM as a regulatory hub of development- and stemness-associated signaling pathways, such as the Wnt, Hedgehog, and Notch pathways, and of DNA DSB repair in cancer cells. The review emphasizes the potential utility of ASPM as a cancer-agnostic and pathway-informed prognostic biomarker and therapeutic target.
Accurate rare variant phasing of whole-genome and whole-exome sequencing data in the UK Biobank
Authors: Robin J. Hofmeister, Diogo M. Ribeiro, Simone Rubinacci, Olivier Delaneau
Journal: Nature Genetics (2023)

Phasing involves distinguishing the two parentally inherited copies of each chromosome into haplotypes. Here, we introduce SHAPEIT5, a new phasing method that quickly and accurately processes large sequencing datasets and applied it to UK Biobank (UKB) whole-genome and whole-exome sequencing data. We demonstrate that SHAPEIT5 phases rare variants with low switch error rates of below 5% for variants present in just 1 sample out of 100,000. Furthermore, we outline a method for phasing singletons, which, although less precise, constitutes an important step towards future developments. We then demonstrate that the use of UKB as a reference panel improves the accuracy of genotype imputation, which is even more pronounced when phased with SHAPEIT5 compared with other methods. Finally, we screen the UKB data for loss-of-function compound heterozygous events and identify 549 genes where both gene copies are knocked out. These genes complement current knowledge of gene essentiality in the human genome.
Error in Results
Journal: JAMA Network Open (2023)

Lina Lundström, MSc; Oskar Flygare, MSc; Erik Andersson, PhD; Jesper Enander, PhD; Matteo Bottai, PhD; Volen Z. Ivanov, PhD; Julia Boberg, MSc; Diana Pascal, MD, PhD; David Mataix-Cols, PhD; Christian Rück, MD, PhD
Exposure of progressive immune dysfunction by SARS-CoV-2 mRNA vaccination in patients with chronic lymphocytic leukemia: A prospective cohort study
Authors: Kai Qin, Kazuhito Honjo, Scott Sherrill-Mix, Weimin Liu, Regina M. Stoltz, Allisa K. Oman, Lucinda A. Hall, Ran Li, Sarah Sterrett, Ellen R. Frederick, Jeffrey R. Lancaster, Mayur Narkhede, Amitkumar Mehta, Foluso J. Ogunsile, Rima B. Patel, Thomas J. Ketas, Victor M. Cruz Portillo, Albert Cupo, Benjamin M. Larimer, Anju Bansal, Paul A. Goepfert, Beatrice H. Hahn, Randall S. Davis
Journal: PLoS Medicine (2023)

Patients with chronic lymphocytic leukemia (CLL) have reduced seroconversion rates and lower binding antibody (Ab) and neutralizing antibody (NAb) titers than healthy individuals following Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) mRNA vaccination. Here, we dissected vaccine-mediated humoral and cellular responses to understand the mechanisms underlying CLL-induced immune dysfunction.
No Association of Preablation Thyroglobulin Antibody Positivity and Outcome in Pediatric Patients With Papillary Thyroid Carcinoma
Authors: Yangmengyuan Xu, Lei Shi, Jie Wu, Huilan Li, Yu Wang, Bin Liu
Journal: Clinical Nuclear Medicine (2023)

Objective This multicenter study was designed to evaluate the relationship between preablation thyroglobulin antibody (TgAb) positivity and clinical outcomes in pediatric patients with papillary thyroid carcinoma (PTC). Methods In the period 2005–2020, all consecutive PTC patients 18 years or younger who underwent total thyroidectomy and radioiodine ablation at 3 tertiary hospitals in southwestern China were retrospectively included. Thyroglobulin antibody was measured before remnant ablation. Tumor characteristics and long-term outcomes were compared between TgAb-positive and TgAb-negative patients. Results One hundred thirty-two patients were analyzed. Preablation TgAb positivity was presented in 37.1% of patients. Tumor characteristics, lymph node metastases, and median duration of follow-up were similar between TgAb-positive and -negative patients. During follow-up, the percentage of patients with either surgical reintervention for lymph node metastases (4.1% vs 4.8%, P = 1.000) or repeated 131 I therapy (14.3% vs 20.5%, P = 0.373) was similar between TgAb-positive and -negative patients. At the final follow-up visit, the rates of structural disease did not differ between the 2 groups (6.1% vs 4.8%, P = 0.710). Conclusions This multicentric study highlights no association of preablation TgAb positivity and clinical outcome in pediatric patients with PTC.
Immunoception: the insular cortex perspective
Authors: Asya Rolls
Journal: Cellular and Molecular Immunology (2023)

Abstract To define the systemic neuroimmune interactions in health and disease, we recently suggested immunoception as a term that refers to the existence of bidirectional functional loops between the brain and the immune system. This concept suggests that the brain constantly monitors changes in immune activity and, in turn, can regulate the immune system to generate a physiologically synchronized response. Therefore, the brain has to represent information regarding the state of the immune system, which can occure in multiple ways. One such representation is an immunengram, a trace that is partially stored by neurons and partially by the local tissue. This review will discuss our current understanding of immunoception and immunengrams, focusing on their manifestation in a specific brain region, the insular cortex (IC).
Disparities in Cardiovascular Health by Food Security Status and Supplemental Nutrition Assistance Program Participation Using Life’s Essential 8 Metrics
Authors: Cindy W. Leung, Julia A. Wolfson, Eric J. Brandt, Eric B. Rimm
Journal: JAMA Network Open (2023)

This cross-sectional study examines the associations among household food security, Supplemental Nutrition Assistance Program participation, and cardiovascular health among 2013-2018 National Health and Nutrition Examination Survey participants.
Disparities in COVID-19 Disease Incidence by Income and Vaccination Coverage — 81 Communities, Los Angeles, California, July 2020–September 2021
Authors: John M. Masterson, Michael Luu, Kai B. Dallas, Lauren P. Daskivich, Brennan Spiegel, Timothy J. Daskivich
Journal: MMWR Morbidity and Mortality Weekly Report (2023)

COVID-19 has disproportionately affected socially vulnerable communities characterized by lower income, lower education attainment, and higher proportions of minority populations, among other factors (1-4). Disparities in COVID-19 incidence and the impact of vaccination on incidence disparities by community income were assessed among 81 communities in Los Angeles, California. Median community vaccination coverage and COVID-19 incidence were calculated across household income strata using a generalized linear mixed effects model with Poisson distribution during three COVID-19 surge periods: two before vaccine availability (July 2020 and January 2021) and the third after vaccines became widely available in April 2021 (September 2021). Adjusted incidence rate ratios (aIRRs) during the peak month of each surge were compared across communities grouped by median household income percentile. The aIRR between communities in the lowest and highest median income deciles was 6.6 (95% CI = 2.8-15.3) in July 2020 and 4.3 (95% CI = 1.8-9.9) in January 2021. However, during the September 2021 surge that occurred after vaccines became widely availabile, model estimates did not identify an incidence disparity between the highest- and lowest-income communities (aIRR = 0.80; 95% CI = 0.35-1.86). During this surge, vaccination coverage was lowest (59.4%) in lowest-income communities and highest (71.5%) in highest-income communities (p<0.001). However, a significant interaction between income and vaccination on COVID-19 incidence (p<0.001) indicated that the largest effect of vaccination on disease incidence occured in the lowest-income communities. A 20% increase in community vaccination was estimated to have resulted in an additional 8.1% reduction in COVID-19 incidence in the lowest-income communities compared with that in the highest-income communities. These findings highlight the importance of improving access to vaccination and reducing vaccine hesitancy in underserved communities in reducing disparities in COVID-19 incidence.